{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T16:10:43Z","timestamp":1789575043359,"version":"build-2803163510"},"reference-count":58,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T00:00:00Z","timestamp":1772496000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>\n                    Gastric cancer has become one of the most common cancers globally. Sapodilla or known as\n                    <jats:italic>Manilkara zapota<\/jats:italic>\n                    (L.) P. Royen, has been traditionally applied for cough, cold, and diarrhea. The detailed mechanisms in modulating sapodilla leaf 70% ethanol extract against HGT-1 human gastric cancer cell line have yet to be fully studied. Apoptosis induction was evaluated using an Annexin V-FITC\/PI staining kit with flow cytometry. Caspase-3 and -8 expression were determined by colorimetric analysis. To explore the molecular mechanisms of action of the 70% ethanol extract of sapodilla leaves in HGT-1 cells, quantitative real-time PCR (qPCR) was performed. Overall analyses demonstrated that sapodilla leaf 70% ethanol extract was cytotoxic and suppressed the growth of HGT-1 cells. The 70% ethanol extract of sapodilla leaves significantly suppressed the proliferation of HGT-1 cells. Moreover, it enhanced the expression of nuclear factor E2-related factor 2 (\n                    <jats:italic>Nrf2<\/jats:italic>\n                    ) and heme oxygenase-1 (\n                    <jats:italic>HO-1<\/jats:italic>\n                    ), while concurrently suppressing the transcriptional activities of nuclear factor-kappa B (\n                    <jats:italic>NF-\u03baB<\/jats:italic>\n                    ) and inducible nitric oxide synthase (\n                    <jats:italic>iNOS<\/jats:italic>\n                    ). Results indicate that sapodilla leaf 70% ethanol extract has an anti-gastric cancer effect via modulation of multiple signaling pathways. Sapodilla leaf 70% ethanol extract demonstrates promising potential as an anti-gastric cancer agent.\n                  <\/jats:p>","DOI":"10.3389\/fphar.2026.1803513","type":"journal-article","created":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T06:47:10Z","timestamp":1772520430000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Induction of apoptosis by ethanol extract of sapodilla leaf in HGT-1 cells involved caspase-independent signal transduction pathway and activation of Nrf2\/HO-1"],"prefix":"10.3389","volume":"17","author":[{"given":"Bee Ling","family":"Tan","sequence":"first","affiliation":[{"name":"Department of Diagnostic and Allied Health Science, Faculty of Health and Life Sciences, Management and Science University (MSU), University Drive","place":["Shah Alam, Selangor, Malaysia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lee Chin","family":"Chan","sequence":"additional","affiliation":[{"name":"Biovalence Sdn. 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